Perhaps penetration into narrow sorting channels is hindered by the size of cross-linked immune complexes, as has been shown for sorting different sizes of cargoes in macrophages (166). vesicles during intracellular transport; and 4) describe the clinical significance of these processes. Models of the intestinal epithelium and other barrier tissues forin vitrotranscytosis studies will also be briefly characterized. Keywords:SARS-CoV-2, COVID-19, coronavirus, intestines, gastrointestinal tract, microfluidics, transcytosis, endocytosis == Introduction == At the moment, it remains unclear whether the gastrointestinal tract can serve as an Rabbit polyclonal to annexinA5 entry portal for SARS-CoV-2; however, fecal-oral transmission is considered likely (1). There is a concern that SARS-CoV-2 transmission may occurviafrozen foods or packaging (2), so the fate of the coronavirus in the intestine Nodakenin is relevant. SARS-CoV-2 RNA was detected in feces of infected people in >50% of cases, and >20% of patients continued to have positive stool results after negative respiratory sample results (3). The SARS-CoV-2 nucleocapsid (N) protein was found in the cytoplasm of gastric, duodenal, and rectal epithelial cells. Viral RNA was also detected in samples of the esophageal mucosa, although the N-protein was not detected in esophageal epithelial cells (3). A systematic review and meta-analysis of 35 studies showed that ~15% of patients had digestive symptoms including nausea, vomiting, and diarrhea, while 10% of patients had gastrointestinal symptoms alone without respiratory features (4). According to electron microscopy and virus culture data, active viral replication of SARS-CoV-2 was detected in both the small and large intestines (5). SARS-CoV-2 cell entry depends on angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) (6), which are both expressed on the luminal surface of cells in the gastrointestinal tract (3,7). SARS-CoV-2 can cause productive infection of human enterocytes (8). These facts support the possibility of fecal-oral transmission of SARS-CoV-2, and underscore the need to elucidate possible mechanisms of coronavirus penetration through tissue barriers, including in the intestine. == Native and Opsonized Coronaviruses == To understand and model the processes of endocytosis and transcytosis of SARS-CoV-2 in the intestine and other barrier organs, it is necessary to have a clear understanding of the structure of native virions, including their size, the number of cell-interacting spikes on the virion surface, the mechanism and stoichiometric ratios in the interaction of spines with receptors and antibodies, and corresponding structural limitations. A combination of cryoelectron tomography and subtomogram averaging for a study of ~2300 intact SARS-CoV-2 virions showed ellipsoidal envelope particles with average diameters of 64.8 11.8, 85.9 9.4, and 96.6 11.8 nm (average SD) for the short, medium, and long axes of the envelope, respectively (9). About 97% of spike (S) protein trimers in this virion sample were in prefusion conformation and 3% in postfusion, with each virion having an average of 26 15 spikes in prefusion conformation and each spike freely changing the angle relative to the virion membrane (9). In another study, the average virion diameter, if taken as spherical, was 91 11 nm, and each virion had 24 9 S-protein trimers, 3% of which were in postfusion conformation. A small sub-population of virions contained only few S trimers, while larger virions contained more S trimers. There was approximately one spike per 1,000 nm2of virus membrane (10). For comparison, there were approximately 10 spikes of the influenza A virus per 1,000 nm2of membrane surface with a virion diameter of 80120 nm (11). That is, the distances between the spikes of the influenza A and SARS-CoV-2 are approximately 11 nm and 35 nm, Nodakenin respectively. In another study, <0.1% of SARS-CoV-2 S-protein trimers were in postfusion conformation, which can be explained by the type of cells in which virions were produced, including the number of receptors and proteases involved in the transition of receptors into postfusion Nodakenin conformation (12). As it was shown, each virion had an average of 40 spikes evenly distributed over the surface without a tendency of agglomeration (12). Each trimer freely bent at an angle to the membrane due to a stalk with three flexible hinges. In contrast to recombinant S-proteins, trimers synthesized in infected cells were much more densely covered with glycans, mainly due to N-glycosylation (12). The free arrangement and.